Pharmaceutical dosage unit form coating process



United States Patent 3,406,031 PHARMACEUTICAL DOSAGE UNIT FORM COATING PROCESS Samuel Lee, Fair Lawn, N.J., assignor to Geigy Chemical Corporation, Greenburgh, N.Y., a corporation of Delaware No Drawing. Filed Aug. 27, 1964, Ser. No. 392,591 10 Claims. (Cl. 106-171) ABSTRACT OF THE DISCLOSURE A liquid composition for the coating of pharmaceutical dosage unit forms comprising (a) from about 0.1 to about 10 parts of a metal salt of a long chain fatty acid which serves as a lubricant, (b) from about .0001 to about 5 parts of a dispersing agent to negate the water repellent properties of the lubricant, (c) from about .01 to about parts of a hydrophilic protective colloid and (d) from about 50 to about 99 parts of a sugar base syrup.

This invention relates to a novel coating composition and a novel method for coating and coloring pharmaceutical dosage unit forms such as tablets, pills, pellets and the like.

customarily, coating processes are divided into five different unit operations, the lines of which may be somewhat arbitrary. Each of these operations consists of a multiplicity of steps. These operations may be designated as waterproofing and sealing, subcoating, rounding and smoothing, coloring and finishing, and polishing and branding.

The invention is not concerned with waterproofing and sealing. Likewise this invention is not directly involved with the last two operations although it has been found that the procedure of polishing and branding is greatly facilitated by the subject invention. This invention is primarily concerned with operations tWo and three wherein the pharmaceutical dosage unit forms are subcoated and subsequently rounded and smoothed.

Subcoating involves alternately wetting the pharmaceutical dosage unit forms with an adhesive subcoating solution .While they are tumbling over each other in a conventional rotating coating pan. In the smoothing and rounding operation, the pharmaceutiral dosage unit forms are replaced in a clean coating pan which is then rotated. While the pharmaceutical dosage unit forms are tumbling over each other, sufficient warm smoothing syrup to cover each tablet with a thin uniform film is added. Often as many as or steps are required during this operation to achieve adequate smoothing and rounding.

Compressed pharmaceutical dosage unit forms are frequently discoid in shape but they may also be ovate, oblong, cylindrical, triangular, rectangular or many other shapes. It is a characteristic of most pharmaceutical dosage unit forms that they contain sharp angles as part of their three dimensional surface. During the coating of these pharmaceutical dosage unit forms, the angular portions of the surface must be completely filled so that the finished surface presents a smooth circumferential arc in all directions.

The coating composition and method of the subject invention are particularly adapted to producing smooth circumferential surfaces on pharmaceutical dosage unit forms in a minimum amount of time. This composition is as follows:

3,406,031 Patented Oct. 15, 1968 Percentages Lubricating compound from about 0.1 to about 10 Dispersing agent from about .0001 to about 5 Colloidal material from about .01 to about 10 Coating vehicle from about 50 to about 99 In the above enumerated composition the lubricating compound is part of the coating composition. The addition of this lubricating compound specifically enhances the passage of the pharmaceutical dosage unit forms over each other in the rotating coating pan and as such superior circumferential surfaces are produced in less time. The presence of a lubricating compound in the coating composition specifically enhances the filling of the angular portions of the pharmaceutical dosage unit form surface so that pleasing circumferential surfaces are produced.

A further advantage of this coating procedure is a marked reduction in the breakage of tablets during coating and a reduction of seconds which must be discarded. During the coating of a conventional batch of a million or more tablets, the physical weight of this large mass of tablets tends to fracture tablets which must then be rejected. This can be prevented conventionally by using greater compression to produce harder tablets, but at a sacrifice of solubility after ingestion. By the composition and method of the subject invention, frangible tablets which readily disintegrate after swallowing, can be coated with minimum breakage.

Among the lubricating compounds which are adapted for use in the subject composition are water insoluble non-toxic light metal salts of long chain fatty acids. Water insoluble non-toxic lubricating compounds specifically adapted to the subject composition are metal salts of long chain fatty acids such as magnesium stearates, oleates, laurates and myristates; aluminum stearates, oleates and myristates; calcium stearates, myristates and laurates; zinc stearates; iron stearates, etc.

The addition of metal salts of long chain fatty acids to pharmaceutical dosage unit form coating compositions has long been known. However, these salts were added to the prior art coating compositions to impart water repellency to special purpose pharmaceutical dosage unit forms such as enteric, delayed action, time release and multiple core products. Due to the water repellency properties, these salts cannot ordinarily be used in the coatings of regular pharmaceutical dosage unit forms which are designed to disintegrate shortly after ingestion. By the composition and method of the subject invention, the lubricating properties of these water insoluble non-toxic metal salts of long chain fatty acids can be utilized without altering the disintegrating characteristics of the pharmaceutical dosage unit forms.

The water repellent properties of the lubricating compound are negated by the addition of a dispersing agent which reduces the surface tension of the water and permits disintegration of the pharmaceutical dosage unit form without delay.

Dispersing agents which will negate the water repellent properties of the lubricating compound include non-toxic surfactants such as sodium 2-ethylhexane sulfonate, sodium di[Z-ethylhexyl]-phosphate, sodium salt of sulfate ester of an alkyl phenoxy polyoxyethylene ethanol, oleic acid ester of sodium isethionate, sodium N-methyl-N-acyl taurate (commercially available mixture), sodium salt of sulfonated lauryl and myristyl collamide, sodium salt of sulfated lauryl and myristyl collamide, sodium alkyl aryl sulfonate (commercially available mixture), dioctyl sodium sulfosuccinate, sodium lauryl sulfate, potassium cetyl sulfate, sodium oleyl sulfate, sodium stearate, potassium oleate, etc.

The coating of pharmaceutical dosage unit forms is enhanced by the presence of an edible hydrophilic protective colloid. Among the water soluble protective colloids adapted to the subject invention are cellulose ethers such as methyl cellulose and hydroxyethyl cellulose; cellulose esters such as carboxymethyl cellulose; natural carbohydrates such as Water soluble salts of alginic acid and acacia; and protein colloids such as casein and albumin.

The coating vehicle comprises 50-90% solution or suspension of sucrose, glucose, dextrose, lactose, fructose, sorbitol or other innocuous materials and mixtures thereof in a volatile solvent such as water, alcohol, etc.

The coating composition of the subject invention may be prepared by dissolving the dispersing agent and lubricating compound in water. The colloidal matter may be added to this solution or to the coating syrup. Upon mixing the water solution and coating syrup an efiicient coating composition is produced which can be used to simultaneously perform the functions of subcoating and coating. If a colored coating is desired an appropriate dye or pigment can be added to the coating composition so that upon subcoating and coating colored pharmaceutical dosage unit forms are produced.

The following examples illustrate coating compositions and coating procedures which are adapted to this invention. These examples are submitted by way of illustration and not limitation.

Example 1 7 Composition: Grams Magnesium stearate 50.0 Sodium lauryl sulfate 10.0 Hydroxy ethyl cellulose 20.0 Water 120.0 Simple syrup U.S.P. 800.0

Procedure.-The sodium lauryl sulfate is dissolved in the water and the magnesium stearate dispersed therein by light speed agitation until a translucent, smooth liquid is obtained free from visible particles. The cellulose compound is dissolved in the syrup by high speed agitation, avoiding the formation of lumps of undissolved colloid. Upon mixing these two colloidal solutions, an efiicient coating vehicle is obtained. Within less than one hour, an entire batch of tablets is smoothly and roundly defined with a colorless, translucent coating.

Example 2 Composition: Grams Aluminum distearate 90 Dioctyl sodium sulfosuccinate 5 Methyl cellulose c.p.s.) 15 Water 290 70% sorbitol solution 200 Sucrose 400 Procedure.The sulfosuccinate is dissolved in the water and the aluminum stearate dispersed therein while mixing. With continued agitation, the methyl cellulose is added and dissolved. The sorbitol solution is then added and the sucrose dissolved in this mixture. When applied to a batch of tablets rotating in a conventional coating pan this mixture will produce a smooth, circumferential coating on each tablet in less than ten steps.

Procedure-The sodium oleate and the albumin are dissolved in the water and the calcium myristate dispersed therein With simple agitation. This dispersion is mixed with the glucose and syrup. The resulting coating mixture is applied to a commercial batch of tablets rotating and tumbling in a conventional coating pan. In less than ten coating steps, a translucent subcoating and smooth coating is obtained which is ready for final coloring, polishing and branding.

Example 4 Composition: Grams Magnesium oleate 60.0 Oleic acid 20.0 Casein 20.0 Potassium hydroxide 2.0 Water 500.0 Sucrose 800.0

Procedure.The oleic acid and casein are dissolved in the aqueous solution of the potassium hydroxide which may be heated to C. The magnesium stearate is dispersed therein and the sucrose dissolved in the dispersion. This coating suspension is ready for use in a conventional coating pan and will afford smoothly rounded tablets completely subcoated in a fraction of the time normally required. In this procedure the dispersing agent is produced in situ by the reaction of oleic acid and potassium hydroxide.

Procedure-The potassium cetyl sulfate and the cellulose gum are dissolved in the Water and the aluminum stearate and titanium dioxide are dispersed therein. The sucrose is dissolved in this mixture and the mannitol incorporated therein. In that this coating mixture contains an inert filler (titanium dioxide), it produces an opaque white subcoating and coating. A round, smooth tablet is produced in 8 or 9 discrete coating steps using a conventional coating pan for even the most angular of tablets.

Example 6 Composition: Grams Iron distearate 30.0 Sodium oleyl sulfate 10.0 Talc 100.0 Sodium alginate 20.0 Water 450.0 Lactose 600.0

Procedure-The sodium oleyl sulfate and alginate are dissolved in the water and the iron distearate and talc are dispersed therein. The sucrose is dissolved in this mixture and the lactose incorporated by agitation. With the talc this mixture will afford an attractive, opaque subcoating and a smooth round coating which can be given a final coloring and polishing in a minimum number of steps.

What is claimed is:

1. A liquid coating composition for the coating of pharmaceutical dosage unit forms consisting essentially of (a) from about 0.1 to about 10 parts of a water insoluble non-toxic light metal salt of a long chain fatty acid, (b) from about .0001 to about 5 parts of a water soluble non-toxic dispersing agent, (c) from about .01 to about parts of a water soluble non-toxic hydrophilic protective colloid and (d) from about 50 to about 99 parts of a sugar base syrup.

2. A liquid coating composition for the coating of pharmaceutical dosage unit forms consisting essentially of (a) from about 0.1 to about 10 parts of a water soluble non-toxic lubricating compound selected from the group consisting of magnesium stearate, magnesium oleate, magnesium laurate, magnesium myristate, aluminum stearate, aluminum oleate, aluminum myristate, calcium stearate, calcium laurate, calcium myristrate, zinc stearate and iron stearate, (b) from about .0001 to about 5 parts of a water soluble non-toxic hydrophilic dispersing agent, (c) from about .01 to about 10 parts of a water soluble non-toxic protective "colloid and (d) from about 50 to about 99 parts of a sugar base syrup.

3. A liquid coating composition for the coating of pharmaceutical dosage unit forms consisting essentially of (a) from about 0.1 to about 10 parts of a water insoluble non-toxic lubricating compound selected from the group consisting of magnesium stearate, magnesium oleate, magnesium laurate, magnesium myristate, aluminum stearate, aluminum oleate, aluminum myristate, calcium stearate, calcium laurate calcium myristate, zinc stearate and iron stearate, (b) from about .0001 to about 5 parts of a water soluble non-toxic dispersing agent selected from the group consisting of sodium 2- ethylhexane sulfonate, sodium di[2-ethylhexyl]-phosphate, sodium salt of sulfate ester of an alkyl phenoxy polyoxyethylene ethanol, oleic acid ester of sodium isethonate, sodium N-methyl-N-acyl taurate, sodium salt of sul-fonated lauryl and myristyl collamide, sodium salt of sulfated lauryl and myristyl collamide, sodium alkyl aryl sulfate, dioctyl sodium sulfosuccinate, sodium lauryl sulfate, potassium cetyl sulfate, sodium oleyl sulfate, sodium stearate and potassium oleate, (c) from about .01 to about 10 parts of a water soluble non-toxic hydrophilic protective colloid and (d) from about 50 to about 99 parts of a sugar base syrup.

4. A liquid coating composition for the coating of pharmaceutical dosage unit forms consisting essentially of (a) from about 0.1 to about 10 parts of a water insoluble non-toxic lubricating compound selected from the group consisting of magnesium stearate, magnesium oleate, magnesium laurate, magnesium myristate, aluminum stearate, aluminum oleate, aluminum myristate, calcium stearate, calcium laurate, calcium myristate, zinc stearate and iron stearate, (b) from about .0001 to about 5 parts of a water soluble non-toxic dispersing agent selected from the group consisting of sodium Z-ethylhexane sulfonate, sodium di[Z-ethylhexyl]-phosphate, sodium salt of sulfate ester of an alkyl phenoxy polyoxyethylene ethanol, oleic acid ester of sodium isethionate, sodium N methyl-Nacyl taurate, sodium salt of sulfonated lauryl and myristyl collamide, sodium salt of sol-fated lauryl and myristyl collamide, sodium alkyl aryl sulfonate, dioctyl sodium sulfosuccinate, sodium lauryl sulfate, potassium cetyl sulfate, sodium oleyl sulfate, sodium stearate and potassium oleate, (c) from about .01 to about 10 parts of a water soluble non-toxic protective colloid selected from the group consisting of methyl cellulose,

hydroxy ethyl cellulose, carboxy methyl cellulose, water soluble salts of alginic acid, acacia, casein, and albumin, (d) from about 50 to about 99 parts of a sugar base syrup.

5. A liquid coating composition for the coating of pharmaceutical dosage unit forms consisting essentially of (a) from about 0.1 to about 10 parts of a water insoluble non-toxic lubricating compound selected from the group consisting of magnesium stearate, magnesium oleate, magnesium laurate, magnesium myristate, aluminum stearate, aluminum oleate, aluminum myristate, calcium stearate, calcium laurate, calcium myristate, zinc stearate and iron stearate, (b) from about .0001 to about 5 parts of a water soluble non-toxic dispersing agent selected from the group consisting of sodium 2-ethylhexane sulfonate, sodium salt of sulfate ester of an alkyl phenoxy polyoxyethylene ethanol, oleic acid ester of sodium isethion-ate, sodium N-methyLN-acyl taurate, sodium salt of sulfonated lauryl and myristyl collamide, sodium salt of sulfated lauryl and myristyl collamide, sodium alkyl aryl sulfonate, dioctyl sodium sulfosuccinate, sodium lauryl sulfate, potassium cetyl sulfate, sodium oleyl sulfate, sodium stearate and postassium oleate, (c) from about .01 to about 10 parts of a water soluble non-toxic protective colloid selected from the group consisting of methyl cellulose, hydroxy ethyl cellulose, carboxy methyl cellulose, water soluble salts of alginic acid, acacia, casein, and albumin and (d) from about 50 to about 99 parts of a sugar base syrup selected from the group consisting of sucrose, glucose, dextrose, lactose, fructose, sorbitol and mixtures thereof.

6. The composition of claim 5 wherein the water insoluble non-toxic lubricating agent is magnesium stearate.

7. The composition of claim 5 wherein the water soluble non-toxic dispersing agent is potassium oleate.

8. The composition of claim 5 wherein the water soluble protective colloid is hydroxy ethyl cellulose.

9. A composition of claim 5 wherein the sugar base is a glucose-sucrose base syrup.

10. A liquid coating composition for the coating of pharmaceutical dosage unit forms consistin essentially of (a) from about .1 to about 10 parts of magnesium stearate, (b) from about .0001 to about 5 parts of potassium oleate, (c) from about .01 to about 10 parts of hydroxy ethyl cellulose and (d) from about 50 to about 99 parts of a glucose-sucrose base syrup.

References Cited UNITED STATES PATENTS 2,684,949 7/1954 McMillan et a1 252-309 2,925,365 2/1960 Nicholson ct a1. 106-209 X 3,043,747 7/1962 Long 106-197 X OTHER REFERENCES F. C. Blubaugh et al.: An Enteric Composition Coating 1, December 1958, J. Am. Pharm. Assoc, Sci. ed., 47, 857, 1958.

JAMES A. SEIDLECK, Primary Examiner.

T. MORRIS, Assistant Examiner.

sodium 'di [2-ethylhexyl'] Thmphate, 

